1. Uric acid induces the expression of TNF‑α via the ROS‑MAPK‑NF‑κB signaling pathway in rat vascular smooth muscle cells.
- Author
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Tang L, Xu Y, Wei Y, and He X
- Subjects
- Animals, Cell Survival drug effects, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Imidazoles pharmacology, Male, Mitogen-Activated Protein Kinases metabolism, Muscle, Smooth, Vascular cytology, Muscle, Smooth, Vascular drug effects, Muscle, Smooth, Vascular metabolism, NF-kappa B antagonists & inhibitors, NF-kappa B metabolism, Pyridines pharmacology, Pyrrolidines pharmacology, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species metabolism, Thiocarbamates pharmacology, Tumor Necrosis Factor-alpha analysis, Tumor Necrosis Factor-alpha genetics, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors, p38 Mitogen-Activated Protein Kinases metabolism, Gene Expression drug effects, Signal Transduction drug effects, Tumor Necrosis Factor-alpha metabolism, Uric Acid pharmacology
- Abstract
Hyperuricemia and artery atherosclerosis are closely associated and, as a classic inflammatory biomarker, tumor necrosis factor‑α (TNF‑α) has a direct role in atherogenesis. In the present study, it was demonstrated that uric acid was capable of inducing the generation of TNF‑α in vascular smooth muscle cells (VSMCs). The expression levels of proteins were detected using enzyme‑linked immunosorbent assays and western blot analysis. The expression levels of mRNAs were determined using reverse transcription‑quantitative polymerase chain reaction analysis, and superoxide anion levels were detected using a fluorescence microscope. From the results, it was concluded that uric acid induced the expression of TNF‑α in the VSMCs. The antioxidant, N‑acetylcysteine, eliminated the uric acid‑induced expression of TNF‑α. In addition, uric acid increased the level of reactive oxygen species (ROS) and activated the phosphorylation of p38. Subsequent experiments confirmed that the p38 mitogen‑activated protein kinase (MAPK) inhibitor, SB203580, and nuclear factor (NF)‑κB inhibitor, pyrrolidine dithiocarbamate, eliminated the uric acid‑induced expression of TNF‑α. It was demonstrated that uric acid induced the expression of TNF‑α via the ROS‑MAPK‑NF‑κB signaling pathway in VSMCs, providing novel evidence supporting the pro‑inflammatory and pro‑atherosclerotic effects of uric acid.
- Published
- 2017
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